SERENA-4: A Comparative Study of AZD9833 Plus Palbociclib Versus Anastrozole Plus Palbociclib in Patients With ER-Positive HER2 Negative Breast Cancer Who Have Not Received Any Systemic Treatment for Advanced Disease.

Sponsor

AstraZeneca (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04711252

Collaborator

(none)

1,402

Enrollment

296

Locations

Arms

96.5

Anticipated Duration (Months)

4.7

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The study is intended to show superiority of AZD9833 in combination with palbociclib (a CDK4/6 inhibitor) versus anastrozole (an aromatase inhibitor) and palbociclib as the initial treatment of patients with hormone receptor-positive (ER-positive), human epidermal growth factor 2-negative (HER2-negative) advanced/metastatic breast cancer.

Condition or Disease	Intervention/Treatment	Phase
ER-Positive HER2-Negative Breast Cancer	Drug: AZD9833 Drug: Anastrozole Drug: Anastrozole placebo Drug: AZD9833 placebo Drug: Palbociclib Drug: Luteinizing hormone-releasing hormone (LHRH) agonist	Phase 3

Detailed Description

A Randomised, Multicentre, Double-Blind, Phase III study will evaluate the safety and efficacy of AZD9833 (next generation oral SERD) in combination with palbociclib versus anastrozole in combination with palbociclib for the treatment of patients with ER-positive breast cancer. The goal of the study is to demonstrate superiority of AZD9833 over anastrozole in the context of combination with palbociclib in first line setting.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

1402 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

SERENA-4: A Randomised, Multicentre, Double-Blind, Phase III Study of AZD9833 (an Oral SERD) Plus Palbociclib Versus Anastrozole Plus Palbociclib for the Treatment of Patients With Estrogen Receptor-Positive, HER2-Negative Advanced Breast Cancer Who Have Not Received Any Systemic Treatment for Advanced Disease

Actual Study Start Date :

Jan 28, 2021

Anticipated Primary Completion Date :

Nov 10, 2025

Anticipated Study Completion Date :

Feb 12, 2029

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AZD9833 + palbociclib The patients will receive AZD9833 (75 mg, PO, once daily) + palbociclib (PO, once daily, 125 mg for 21 consecutive days followed by 7 days off treatment) + anastrozole placebo (1 mg, PO, once daily)	Drug: AZD9833 Dosage formulation: AZD9833 tablets will be administered orally Drug: Anastrozole placebo Dosage formulation: anastrozole placebo tablets will be administrated orally. Drug: Palbociclib Dosage formulation: palbociclib tablets/capsules will be administered orally Drug: Luteinizing hormone-releasing hormone (LHRH) agonist Men (when medically applicable) and pre- or peri-menopausal women are required to receive a monthly LHRH agonist.
Active Comparator: Anastrozole + palbociclib The patients will recieve Anastrozole (1 mg, PO, once daily) + palbociclib (PO, once daily, 125 mg for 21 consecutive days followed by 7 days off treatment) + AZD9833 placebo (PO, once daily)	Drug: Anastrozole Dosage formulation: Anastrozole tablets will be administered orally. Drug: AZD9833 placebo Dosage formulation: AZD9833 placebo tablets will be administrated orally. Drug: Palbociclib Dosage formulation: palbociclib tablets/capsules will be administered orally Drug: Luteinizing hormone-releasing hormone (LHRH) agonist Men (when medically applicable) and pre- or peri-menopausal women are required to receive a monthly LHRH agonist.

Arm

Intervention/Treatment

Experimental: AZD9833 + palbociclib

The patients will receive AZD9833 (75 mg, PO, once daily) + palbociclib (PO, once daily, 125 mg for 21 consecutive days followed by 7 days off treatment) + anastrozole placebo (1 mg, PO, once daily)

Drug: AZD9833

Dosage formulation: AZD9833 tablets will be administered orally

Drug: Anastrozole placebo

Dosage formulation: anastrozole placebo tablets will be administrated orally.

Drug: Palbociclib

Dosage formulation: palbociclib tablets/capsules will be administered orally

Drug: Luteinizing hormone-releasing hormone (LHRH) agonist

Men (when medically applicable) and pre- or peri-menopausal women are required to receive a monthly LHRH agonist.

Active Comparator: Anastrozole + palbociclib

The patients will recieve Anastrozole (1 mg, PO, once daily) + palbociclib (PO, once daily, 125 mg for 21 consecutive days followed by 7 days off treatment) + AZD9833 placebo (PO, once daily)

Drug: Anastrozole

Dosage formulation: Anastrozole tablets will be administered orally.

Drug: AZD9833 placebo

Dosage formulation: AZD9833 placebo tablets will be administrated orally.

Drug: Palbociclib

Dosage formulation: palbociclib tablets/capsules will be administered orally

Drug: Luteinizing hormone-releasing hormone (LHRH) agonist

Men (when medically applicable) and pre- or peri-menopausal women are required to receive a monthly LHRH agonist.

Outcome Measures

Primary Outcome Measures

Progression-free survival (PFS) assessed by the Investigator as defined by response evaluation criteria in solid tumors (RECIST) version 1.1 [From randomization until progression per RECIST 1.1 as assessed by the investigator at local site or death due to any cause (up to 5 years)]
PFS is defined as the time from randomization to objective disease progression (as assessed by RECIST) or death.

Secondary Outcome Measures

Overall survival (OS) [From randomization until the date of death due to any cause (up to 8 years)]
The OS is defined as the time from randomization to death due to any cause.
Second progression-free survival (PFS2) [From randomization to the earliest of the progression event (following the initial progression), subsequent to first subsequent therapy or death (up to 5 years)]
Time to second progression or death (PFS2) will be defined as the time from randomisation to the earliest of the progression event (following the initial progression), subsequent to first subsequent therapy or death.
Objective response rate (ORR) assessed by the Investigator as defined by RECIST version 1.1 [From randomization until a response or in the absence of a response from randomization up until progression, or the last evaluable assessment in the absence of progression (up to 5 years)]
ORR is defined as the proportion of patients who have a CR or partial response, as determined by the investigator at local site per RECIST 1.1.
Duration of response (DoR) assessed by the Investigator as defined by RECIST version 1.1 [From the date of first documented response until date of documented progression per RECIST 1.1 as assessed by the investigator at local site or death due to any cause (up to 5 years)]
The DoR will be defined as the time from the date of first documented response until date of documented progression or death in the absence of disease progression.
Time to chemotherapy (TTC) [From randomization until the earlier of the start date of chemotherapy or death due to any cause (up to 5 years)]
Time to chemotherapy is defined as the time from randomization until the earlier of the start date of chemotherapy or death due to any cause.
Time to first subsequent anti-cancer therapy (TFST) [From randomization until the earlier of start date of the first subsequent anti-cancer therapy after discontinuation of randomized treatment, or death due to any cause (up to 5 years)]
TFST is defined as time from randomization until the earlier of start date of the first subsequent anti-cancer therapy after discontinuation of randomized treatment, or death due to any cause.
Clinical benefit rate at 24 weeks (CBR24) [At least 23 weeks after randomisation]
CBR at 24 weeks is defined as the percentage of participants who have a complete response (CR) or partial response or who have stable disease (SD) per RECIST 1.1 as assessed by the investigator at local site for at least 23 weeks after randomization (to allow for an early assessment within the assessment window).
Time to second subsequent therapy (TSST) [From randomization until the earlier of start date of the second subsequent anti-cancer therapy after discontinuation of first subsequent treatment, or death due to any cause (up to 5 years)]
TSST is defined as time from randomization until the earlier of start date of the second subsequent anti-cancer therapy after discontinuation of first subsequent treatment, or death due to any cause.
Plasma concentration of AZD9833 at specified timepoints [on Day 15]
To assess the steady state PK of AZD9833 in combination with palbociclib in all participants who receive at least one dose of AZD9833 per the protocol, for whom there are at least one reportable PK concentration.
Change from baseline in EORTC QLQ-C30 scale scores [From baseline to 24 weeks post progression (up to approximately 5 years)]
Change from baseline in EORTC QLQ-C30 scale scores for each patient at each post-baseline visit. The comparison will include all randomised patients, as randomised, with baseline and at least one post-baseline visit score for the scale score.
Change from baseline in EORTC QLQ-BR45 scale scores [From baseline to 24 weeks post progression (up to approximately 5 years)]
Change from baseline in EORTC QLQ-BR45 scale scores for each patient at each post-baseline visit. The comparison will include all randomised patients, as randomised, with baseline and at least one post-baseline visit score for the scale score.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 130 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion criteria:

Pre-/peri-menopausal women or men can be enrolled if amenable to be treated with concomitant, approved LHRH agonists for the duration of the study treatment.
De novo Stage 4 disease, or recurrence from early stage disease after standard adjuvant endocrine therapy meeting either one of the following criteria:

Received at least 24 months of AI treatment as part of their adjuvant therapy and at least 12 months have elapsed since the patient's last dose of adjuvant AI therapy without disease progression on treatment
Received at least 24 months of tamoxifen treatment as part of their adjuvant endocrine therapy

Histologically or cytologically documented diagnosis of ER+, HER2-negative breast cancer based on local laboratory results.
Previously untreated with any systemic anti-cancer therapy for their locoregionally recurrent or metastatic ER+ disease.
Measurable disease as defined per RECIST v.1.1 OR at least one lytic or mixed (lytic + sclerotic) bone lesion that can be assessed by CT or MRI.
Eastern Cooperative Oncology Group performance status of 0 or 1.
Adequate organ and marrow function.
Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

Exclusion criteria:

Previous neoadjuvant or adjuvant treatment with an AI treatment +/- CDK4/6 inhibitor with disease recurrence while on or within 12 months of completing treatment.
Previous treatment with AZD9833.
Participation in another clinical study with a study treatment or investigational medicinal device administered in the last 4 weeks prior to randomization or concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.
Advanced, symptomatic, visceral spread, that are at risk of life-threatening complications in the short term.
Known active uncontrolled or symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease.
Any clinically important and symptomatic heart disease .
Currently pregnant (confirmed with positive pregnancy test) or breast-feeding.
As judged by the investigator, any evidence of diseases (such as severe or uncontrolled systemic diseases, renal transplant and active bleeding diseases) which, in the investigator's opinion, makes it undesirable for the participant to participate in the study or that would jeopardize compliance with the protocol.
Any concurrent anti-cancer treatment.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Mobile	Alabama	United States	36604
2	Research Site	Springdale	Arkansas	United States	72762
3	Research Site	Harbor City	California	United States	90710
4	Research Site	Lone Tree	Colorado	United States	80124
5	Research Site	Fort Myers	Florida	United States	33901-8101
6	Research Site	Jacksonville	Florida	United States	32224
7	Research Site	West Palm Beach	Florida	United States	33401
8	Research Site	Evergreen Park	Illinois	United States	60805
9	Research Site	Urbana	Illinois	United States	61801
10	Research Site	Fort Wayne	Indiana	United States	46845
11	Research Site	Lexington	Kentucky	United States	40513
12	Research Site	Baton Rouge	Louisiana	United States	70809
13	Research Site	Baltimore	Maryland	United States	21201
14	Research Site	Silver Spring	Maryland	United States	20904
15	Research Site	Boston	Massachusetts	United States	02114
16	Research Site	Detroit	Michigan	United States	48202
17	Research Site	Rochester	Minnesota	United States	55905
18	Research Site	Hattiesburg	Mississippi	United States	39401
19	Research Site	Jackson	Mississippi	United States	39213
20	Research Site	Hackensack	New Jersey	United States	07601
21	Research Site	Syracuse	New York	United States	13210
22	Research Site	Asheville	North Carolina	United States	28806
23	Research Site	Fargo	North Dakota	United States	58102
24	Research Site	Cincinnati	Ohio	United States	45219
25	Research Site	Cincinnati	Ohio	United States	45267
26	Research Site	Portland	Oregon	United States	97239
27	Research Site	Greenville	South Carolina	United States	29605
28	Research Site	Greenville	South Carolina	United States	29607
29	Research Site	West Columbia	South Carolina	United States	29169
30	Research Site	Rapid City	South Dakota	United States	57701
31	Research Site	Sioux Falls	South Dakota	United States	57105
32	Research Site	Chattanooga	Tennessee	United States	37404
33	Research Site	Nashville	Tennessee	United States	37203
34	Research Site	Austin	Texas	United States	78731
35	Research Site	Houston	Texas	United States	77090
36	Research Site	Tyler	Texas	United States	75702
37	Research Site	Fairfax	Virginia	United States	22031
38	Research Site	Everett	Washington	United States	98201
39	Research Site	Kennewick	Washington	United States	99336
40	Research Site	Renton	Washington	United States	98055
41	Research Site	Morgantown	West Virginia	United States	26505
42	Research Site	Feldkirch		Austria	6807
43	Research Site	Salzburg		Austria	5020
44	Research Site	Wien		Austria	1090
45	Research Site	Wien		Austria	1130
46	Research Site	Anderlecht		Belgium	1070
47	Research Site	Edegem		Belgium	2650
48	Research Site	Gent		Belgium	9000
49	Research Site	Leuven		Belgium	3000
50	Research Site	Liège		Belgium	4000
51	Research Site	Sint-Niklaas		Belgium	9100
52	Research Site	Panagyurishte		Bulgaria	4500
53	Research Site	Plovdiv		Bulgaria	4000
54	Research Site	Plovdiv		Bulgaria	4109
55	Research Site	Shumen		Bulgaria	9700
56	Research Site	Sofia		Bulgaria	1303
57	Research Site	Sofia		Bulgaria	1330
58	Research Site	Sofia		Bulgaria	1407
59	Research Site	Sofia		Bulgaria	1431
60	Research Site	Varna		Bulgaria	9010
61	Research Site	Edmonton	Alberta	Canada	T6G 1Z2
62	Research Site	Vancouver	British Columbia	Canada	V5Z 1H7
63	Research Site	Kitchener	Ontario	Canada	N2G 1G3
64	Research Site	London	Ontario	Canada	N6A 5W9
65	Research Site	Sudbury	Ontario	Canada	P3E 5J1
66	Research Site	Chicoutimi		Canada	G7H 5H6
67	Research Site	Montreal		Canada	H3T 1E2
68	Research Site	Baoding		China	071000
69	Research Site	Beijing		China	100039
70	Research Site	Beijing		China	100142
71	Research Site	Beijing		China
72	Research Site	Bengbu		China	233060
73	Research Site	Changchun		China	130000
74	Research Site	Changchun		China	130021
75	Research Site	Changsha		China	410013
76	Research Site	Chengdu		China	610042
77	Research Site	Chengdu		China	610072
78	Research Site	Chongqing		China	400010
79	Research Site	Dalian		China	116011
80	Research Site	Guangzhou		China	510060
81	Research Site	Guangzhou		China	510100
82	Research Site	Guiyang		China	550004
83	Research Site	Haikou		China	570311
84	Research Site	Hangzhou		China	310009
85	Research Site	Hangzhou		China	310020
86	Research Site	Hangzhou		China	310022
87	Research Site	Hefei		China	230031
88	Research Site	Jinan		China	2501117
89	Research Site	Lanzhou		China	730000
90	Research Site	Linyi		China	276000
91	Research Site	Nanchang		China	330009
92	Research Site	Nanjing		China	210008
93	Research Site	Qingdao		China	266071
94	Research Site	Shanghai		China	200025
95	Research Site	Shanghai		China	200032
96	Research Site	Shanghai		China	200433
97	Research Site	Shenyang		China	110001
98	Research Site	Tianjin		China	300060
99	Research Site	Urumqi		China	830000
100	Research Site	Wuhan		China	430000
101	Research Site	Wuhan		China	430022
102	Research Site	Xi'an		China	710061
103	Research Site	Zhengzhou		China	450008
104	Research Site	Horovice		Czechia	268 01
105	Research Site	Hradec Kralove		Czechia	500 05
106	Research Site	Novy Jicin		Czechia	741 01
107	Research Site	Olomouc		Czechia	775 20
108	Research Site	Praha 10		Czechia	100 34
109	Research Site	Praha 4		Czechia	140 00
110	Research Site	Praha 5		Czechia	150 06
111	Research Site	Besancon Cedex		France	25030
112	Research Site	Bordeaux		France	33030
113	Research Site	Brest Cedex		France	29609
114	Research Site	Caen Cedex 05		France	14076
115	Research Site	Dijon		France	21079
116	Research Site	Le Mans		France	72000
117	Research Site	Lille		France	59000
118	Research Site	Montpellier		France	34070
119	Research Site	Pierre Benite Cedex		France	69495
120	Research Site	Plerin SUR MER		France	22190
121	Research Site	Saint-cloud		France	92210
122	Research Site	Vandoeuvre Les Nancy		France	54000
123	Research Site	Villejuif Cedex		France	94805
124	Research Site	Berlin		Germany	13125
125	Research Site	Bottrop		Germany	46236
126	Research Site	Dessau-RoBlau		Germany	06847
127	Research Site	Essen		Germany	45136
128	Research Site	Freiburg		Germany	79110
129	Research Site	Mönchengladbach		Germany	41061
130	Research Site	München		Germany	81675
131	Research Site	Regensburg		Germany	93053
132	Research Site	Velbert		Germany	42551
133	Research Site	Wuerzburg		Germany	97080
134	Research Site	Budapest		Hungary	1062
135	Research Site	Budapest		Hungary	1088
136	Research Site	Budapest		Hungary	1122
137	Research Site	Debrecen		Hungary	4032
138	Research Site	Győr		Hungary	9024
139	Research Site	Miskolc		Hungary	3526
140	Research Site	Nyíregyháza		Hungary	4400
141	Research Site	Szekszárd		Hungary	7100
142	Research Site	Tatabánya		Hungary	2800
143	Research Site	Zalaegerszeg		Hungary	8900
144	Research Site	Ahmedabad		India	380060
145	Research Site	Bangalore		India	560027
146	Research Site	Calicut		India	673601
147	Research Site	Faridabad		India	121001
148	Research Site	Gurgaon		India	122001
149	Research Site	Karamsad		India	388325
150	Research Site	Kolkata		India	700160
151	Research Site	Madurai		India	625107
152	Research Site	Mumbai		India	400053
153	Research Site	Nagpur		India	440001
154	Research Site	Nashik		India	422009
155	Research Site	Nashik		India	422011
156	Research Site	New Delhi		India	11029
157	Research Site	Rohini		India	110 085
158	Research Site	Bergamo		Italy	24127
159	Research Site	Genova		Italy	16132
160	Research Site	Modena		Italy	41124
161	Research Site	Napoli		Italy	80131
162	Research Site	Novara		Italy	28100
163	Research Site	Padova		Italy	35128
164	Research Site	Parma		Italy	43100
165	Research Site	Prato		Italy	59100
166	Research Site	Roma		Italy	00168
167	Research Site	Rozzano		Italy	20089
168	Research Site	Chiba-shi		Japan	260-8717
169	Research Site	Chuo-ku		Japan	104-0045
170	Research Site	Chuo-ku		Japan	862-8655
171	Research Site	Fukushima-shi		Japan	960-1295
172	Research Site	Hidaka-shi		Japan	350-1298
173	Research Site	Hirakata-shi		Japan	573-1191
174	Research Site	Isehara-shi		Japan	259-1193
175	Research Site	Kitaadachi-gun		Japan	362-0806
176	Research Site	Koto-ku		Japan	135-8550
177	Research Site	Kumamoto-shi		Japan	860-8556
178	Research Site	Kurashiki shi		Japan	701 0192
179	Research Site	Kurume-shi		Japan	830-0013
180	Research Site	Kyoto-shi		Japan	606-8507
181	Research Site	Nagoya-shi		Japan	464-8681
182	Research Site	Nagoya-shi		Japan	467-0001
183	Research Site	Nishinomiya-shi		Japan	663-8501
184	Research Site	Osaka-shi		Japan	540-0006
185	Research Site	Osaka-shi		Japan	541-8567
186	Research Site	Ota-shi		Japan	373-8550
187	Research Site	Sagamihara-shi		Japan	252-0375
188	Research Site	Sapporo-shi		Japan	003-0804
189	Research Site	Sendai-shi		Japan
190	Research Site	Shimotsuke-shi		Japan	329-0498
191	Research Site	Shinagawa-ku		Japan	142-8666
192	Research Site	Shinjuku-ku		Japan	162-8655
193	Research Site	Suita-shi		Japan	565-0871
194	Research Site	Takasaki-shi		Japan	370-0829
195	Research Site	Tsu-shi		Japan	514-8507
196	Research Site	Tsukuba-shi		Japan	305-8576
197	Research Site	Yokohama-shi		Japan	241-8515
198	Research Site	Busan		Korea, Republic of	49201
199	Research Site	Daegu		Korea, Republic of	41404
200	Research Site	Goyang-si		Korea, Republic of	10408
201	Research Site	Incheon		Korea, Republic of	22332
202	Research Site	Seoul		Korea, Republic of	03080
203	Research Site	Seoul		Korea, Republic of	03722
204	Research Site	Seoul		Korea, Republic of	05505
205	Research Site	Seoul		Korea, Republic of	06273
206	Research Site	Seoul		Korea, Republic of	06351
207	Research Site	George Town		Malaysia	10450
208	Research Site	Johor Bahru		Malaysia	81100
209	Research Site	Kuala Lumpur		Malaysia	50586
210	Research Site	Kuala Lumpur		Malaysia	59100
211	Research Site	Kuching		Malaysia	93586
212	Research Site	Selangor		Malaysia	62250
213	Research Site	Del. Cuauhtemoc		Mexico	06700
214	Research Site	Estado de México		Mexico	50080
215	Research Site	La Paz		Mexico	23040
216	Research Site	Metepec		Mexico	52140
217	Research Site	Mexico		Mexico	01710
218	Research Site	MEX		Mexico	14080
219	Research Site	Monterrey		Mexico	64710
220	Research Site	Puebla		Mexico	72424
221	Research Site	Drammen		Norway	3004
222	Research Site	Oslo		Norway	N-0379
223	Research Site	Gdynia		Poland	81-519
224	Research Site	Konin		Poland	62-500
225	Research Site	Koszalin		Poland	75-581
226	Research Site	Lublin		Poland	20-090
227	Research Site	Olsztyn		Poland	10-513
228	Research Site	Rzeszów		Poland	35-001
229	Research Site	Skórzewo		Poland	60-185
230	Research Site	Łódź		Poland	90-302
231	Research Site	Braga		Portugal	4710
232	Research Site	Guimarães		Portugal	4835-044
233	Research Site	Lisboa		Portugal	1400-038
234	Research Site	Lisboa		Portugal	1500-650
235	Research Site	Lisboa		Portugal	1649-035
236	Research Site	Lisboa		Portugal	1998-018
237	Research Site	Loures		Portugal	2674-514
238	Research Site	Porto		Portugal	4099-001
239	Research Site	Porto		Portugal	4200-319
240	Research Site	Porto		Portugal	4200-319
241	Research Site	Vila Nova de Gaia		Portugal	4434-502
242	Research Site	Kaluga		Russian Federation	248007
243	Research Site	Kislino Village, Ryshkovsky Ru		Russian Federation	305524
244	Research Site	Moscow		Russian Federation	111123
245	Research Site	Moscow		Russian Federation	115478
246	Research Site	Moscow		Russian Federation	117997
247	Research Site	Moscow		Russian Federation	121467
248	Research Site	Saint Petersburg		Russian Federation	197758
249	Research Site	Saint-Petersburg		Russian Federation	190103
250	Research Site	Saint-Petersburg		Russian Federation	195067
251	Research Site	Banská Bystrica		Slovakia	974 01
252	Research Site	Bratislava		Slovakia	81250
253	Research Site	Bratislava		Slovakia	833 01
254	Research Site	Košice		Slovakia	041 91
255	Research Site	Prešov		Slovakia	081 81
256	Research Site	Trencin		Slovakia	91171
257	Research Site	Trnava		Slovakia	91708
258	Research Site	Žilina		Slovakia	012 07
259	Research Site	Barcelona		Spain	08908
260	Research Site	Barcelona		Spain	8035
261	Research Site	Jaén		Spain	23007
262	Research Site	Lleida		Spain	25198
263	Research Site	Madrid		Spain	28040
264	Research Site	Madrid		Spain	28046
265	Research Site	Malaga		Spain	29010
266	Research Site	Pamplona		Spain	31008
267	Research Site	Sevilla		Spain	41013
268	Research Site	Valencia		Spain	46015
269	Research Site	Basel		Switzerland	4031
270	Research Site	Bern		Switzerland	3010
271	Research Site	Zürich		Switzerland	8038
272	Research Site	Kaohsiung		Taiwan	824
273	Research Site	Kaohsiung		Taiwan
274	Research Site	Taichung		Taiwan	40443
275	Research Site	Tainan		Taiwan	70403
276	Research Site	Taipei City		Taiwan	110
277	Research Site	Taipei		Taiwan	10048
278	Research Site	Taipei		Taiwan	104
279	Research Site	Taipei		Taiwan	235
280	Research Site	Taoyuan		Taiwan	333
281	Research Site	Adana		Turkey	01120
282	Research Site	Ankara		Turkey	06010
283	Research Site	Ankara		Turkey	06230
284	Research Site	Ankara		Turkey	06340
285	Research Site	Ankara		Turkey	6100
286	Research Site	İstanbul		Turkey	34457
287	Research Site	Izmir		Turkey	35100
288	Research Site	Izmir		Turkey	35620
289	Research Site	Kayseri		Turkey	38039
290	Research Site	Birmingham		United Kingdom	B15 2TH
291	Research Site	Cambridge		United Kingdom	CB2 2QQ
292	Research Site	Colchester		United Kingdom	CO4 5JL
293	Research Site	Leeds		United Kingdom	LS9 7TF
294	Research Site	Northwood		United Kingdom	HA6 2RN
295	Research Site	Nottingham		United Kingdom	NG5 1PB
296	Research Site	Surrey		United Kingdom	GU2 7XX